PD Dr. Tobias P. Dick

Redox-sensitive cysteine residues (yellow) can act as molecular switches

Elevated generation of oxidants (reactive oxygen species) is associated with inflammation and many age-related disorders, including malignancy. Correspondingly, oxidants have been mostly regarded as unwanted and damaging products. However, more recently, it has become clear that some oxidants, in particular hydrogen peroxide (H2O2), also play beneficial roles as signaling molecules in healthy cells. Oxidants regulate adaptive stress responses and cell fate decisions through post-translational modification of transcription factors and other target proteins. In particular, the signaling functions of oxidants are typically based on the reversible oxidation of protein thiol residues, leading to transient activation or inactivation of individual enzymes. In our laboratory we are investigating signaling pathways by which H2O2 contributes to the regulation of cellular physiology. We are interested in the nature of redox alterations that accompany chronic inflammation and malignant growth. Special attention is devoted to the molecular mechanisms by which oxidants achieve specificity as signaling molecules. Another focus is the effort to uncover the spatio-temporal dynamics of oxidative processes in vivo.

The role of H2O2 sensing and signaling in inflammation: H2O2 is released during tissue injury and may act as one of the early signals for the recruitment and activation of immune cells. Recently, we identified H2O2-sensitive proteins involved in inflammatory signaling. We aim to understand the specific links between inflammatory activators, H2O2 and immune effector mechanisms.
Redox homeostasis in tumor cells: Many, if not most, tumor cells differ in redox homeostasis as compared to their normal counterparts. More detailed understanding of these differences may lead to new ideas of how to interfere with tumor growth.
Molecular mechanisms of oxidative signaling: How are H2O2-sensitive signaling proteins oxidized in an efficient and specific manner? Growing evidence suggests that certain peroxidases act as primary oxidant receptors and pass on oxidizing equivalents to specific target proteins.
Monitoring redox changes in cells, tissues and organisms: We recently developed genetically-encoded biosensors for oxidized glutathione and H2O2. A major application is to monitor redox processes as they occur in the physiological context of the whole organism.
Fundamental principles of redox homeostasis: The glutathione system is central to eukaryotic redox homeostasis and drug resistance but remains incompletely understood. We are combining redox imaging and reverse genetics in the model eukaryote S. cerevisiae to uncover fundamental regulatory principles of the glutathione system.